The confounding effects of microvascular physiology on the uptake and diagnostic accuracy of [18F]fluoroethyl-tyrosine positron emission tomography in gliomas

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Abstract Purpose To investigate the physiological influence of tissue perfusion and permeability on O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ([ 18 F]FET) uptake in gliomas by simultaneous MRI dynamic contrast enhanced (DCE) perfusion imaging and the impact of vascular contributions on diagnostic accuracy. Methods Dynamic [ 18 F]FET PET/MRI scans from 50 patients with glioma WHO grade 2–4 were analysed. In each patient multiple subvolumes were delineated to account for intra-patient heterogeneity. Associations of 20–40 min. [ 18 F]FET tumour-to-background ratio (TBR med ) with median blood volume (CBV), blood flow (F), and permeability (Ki) within 134 lesion subvolumes were investigated in linear mixed models. Also, associations with initial area under curve (iAUC 120 ), time to peak (TTP) and slope (Slope 20 − 40 ) from time activity curve were investigated. The influence of adjusting TBR med for microvascular physiological parameters on the diagnostic accuracy for tumour recurrences was assessed in an independent dataset ( n = 61 lesions from 48 patients). Results CBV, F and Ki individually accounted for 42%, 36% and 26%, respectively, of the overall variance in TBR med . DCE metrics combined accounted for 49% of the total variance and for 65% of the regional variance in TBR med . All DCE metrics were associated positively with iAUC 120 and negatively with both Slope 20 − 40 and TTP ( p < 0.001 for all). Adjusting TBR med for microvascular effects lowered TBR by 24% on average and reduced the diagnostic accuracy (ROC AUC) from 0.90 to 0.77 in the test dataset. Conclusion Microvascular properties may contribute to a considerable fraction of the clinical [ 18 F]FET measures in patients with gliomas, and contribute positively to diagnostic performance of [ 18 F]FET PET imaging.

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